Chin-chiu (qinjiao; root of Gentiana macrophylla; see Figure 1) is frequently recommended for treating deficiency heat syndromes involving liver/gallbladder fire. Deficiency heat refers to a heat syndrome that arises because of deficiency in the cooling, moisturizing yin essences or where this deficiency is caused by a prolonged disease of hot nature that damages the yin essences. Usually, these patients are in a weakened condition and also suffer from some degree of qi deficiency. Liver/gallbladder fire represents one major subset of fire syndromes, where these organs (as functionally defined by the traditional Chinese system) participate directly in the pathology. It is said that the liver has a natural tendency to become overheated, so this is an organ that is easily stirred to generate fire when a pathogen reaches the central viscera. Chin-chiu is included in prescriptions that contain mild-natured heat clearing herbs that will be tolerated by the weakened patient; these herbs are usually accompanied by tonics, especially those that nourish yin and blood.

Chin-chiu is categorized in the Materia Medica with the herbs that expel wind-dampness, which are the ones primarily used in treatment of rheumatism: this is just one of the applications of chin-chiu. The liver is said to nourish the tendons and ligaments; chin-chiu is particularly used in cases where these connective tissues become hypercontracted due to insufficient nourishment (e.g., deficiency of liver yin), yielding spasms that run from the joints to the muscles. It is claimed that, unlike most other herbs used for wind-damp syndromes, which typically have a drying nature, this one does not damage the yin (1).

Chin-chiu is as often indicated for "bone fever." This strange term refers to syndromes with fever and sweating in which the person feels as if there is steam coming from the bones, heating up the skin. The Advanced Textbook on Traditional Chinese Medicine and Pharmacology (2) states: "As deficiency of yin gives rise to internal heat which steams inside, a burning sensation in the chest, palms, and soles appears; if the fire goes upward, malar flush occurs."

In the past, the most common disease calling for chin-chiu was probably tuberculosis. This disease, in the absence of effective early treatment, is consumptive in nature. The person becomes very deficient, experiences night sweats, intermittent fevers, and weakness. In modern times, where antibiotics often control the feverish and consumptive diseases, chin-chiu is being used for non-fever diseases, particularly autoimmune disorders, such as lupus. The autoimmune diseases that affect the connective tissues (of which lupus is a prime example) count as deficiency heat syndromes during their active, inflammatory stage.

Gentiana (longdan or longdancao; root of Gentiana scabra; see Figure 2) is a related herb that is stronger in its heat clearing actions and classified with the herbs for clearing heat and drying dampness. Gentiana is often used in the treatment of excess-type liver syndrome, with fire flaring upward to cause red face, red eyes, headache, and hypertensive symptoms (including tinnitus that sounds like rushing waves). Gentiana is especially used when damp-heat congests the liver and gallbladder. This can cause swelling and pain in the region of the liver accompanied by jaundice (i.e., hepatitis) or the heat and dampness may flow downward to cause swellings and sores in the lower body (such as modern use in treating genital herpes). As stated in the Advanced Textbook:

The liver meridian curves around the external genitalia. The damp-heat goes downward along the meridian to permeate the scrotum, thus causing eczema with unbearable itching. Steaming of the testes stagnates the circulation of qi and blood and, therefore, manifests itself as swelling and burning pain of the testes. If the vagina is steamed by damp-heat, yellow and foul leukorrhea and pruritis vulvae appear.

Like chin-chiu, gentiana is included in some formulas for treating rheumatism; like gentiana, chin-chiu is used in some formulas for treating hepatitis. Gentiana is selected for the cases of excess and chin-chiu for the cases of deficiency heat. Both chin-chiu and gentiana were described in the Shennong Bencao Jing (3):

Chin-chiu is bitter and balanced. It mainly treats cold and heat, evil qi, and cold-damp-wind impediment with pain in the limb joints. It precipitates water and disinhibits urination.

Gentiana is bitter and astringent. It mainly treats cold and heat in the bones, fright epilepsy, and evil qi. It mends expiry and damage, settles the five viscera, and kills gu toxins.

These descriptions are somewhat similar, with chin-chiu specified for treating dampness and getting rid of excess water, and gentiana specified for agitation and fright, and for getting rid of gu toxins, a group of pathogens that appears to correspond mainly to parasites. The calming effect of gentiana is related to its ability to purge excess liver fire that binds up the flow of qi. As stated in the Advanced Textbook: "Once the function of the liver in promoting the free flow of qi is impeded, irritability and easy anger may result. Disturbance of the mind by fire-heat produces insomnia and dream-disturbed sleep."

In the revision of the Materia Medica by Tao Hongjing (ca. 500 A.D.), gentiana was categorized with the "upper class" herbs and said to be of benefit for health and longevity with prolonged use. Today, the situation is different: caution is expressed over this very bitter herb, for fear that it will damage the spleen/stomach system and cause diarrhea if the dosage is too high or if it is taken for too long. By contrast, chin-chiu was categorized by Tao with the "middle class" of herbs, indicating that it would be useful in treating diseases, but not of value for prolonged administration to attain long life. This is consistent with the modern understanding of the herb, though it is believed that chin-chiu, unlike gentiana, can be administered over a prolonged period, as may be necessary to treat chronic diseases, such as rheumatoid arthritis.

Chin-chiu is named for its original main growing location, Jinzhong (Chin-chung in Wade-Giles transliteration), in Shanxi Province (4). The root is in the form of a mass of small intertwined rootlets: the character for jiao, or chiu in Wade-Giles transliteration, is derived from the character jiu, for the number 9 also meaning many, with a "grass radical" above, indicating that it makes reference to a plant name. Gentiana is named for its extreme bitter taste: longdan means dragon's bile (cao means weed). In the Chinese pharmacies, chin-chiu is provided in thin slices from the main part of the root (see Figure 3); the numerous entangled root ends are more easily seen in longdancao, which is kept whole (see Figure 4).

USE IN TRADITIONAL FORMULAS

Gentiana is an ingredient in several traditional formulas, but most references to use of this herb are associated with the well-known Longdan Xiegan Tang, commonly called Gentiana Combination (longdan = gentiana; xiegan = cleanse the liver, referring to clearing liver fire; tang = decoction). This extremely bitter formula has become widely used as a pill as well as the decoction. In virtually all clinical reference books, this formula is mentioned among the first possibilities for treating any syndrome of liver fire or liver/gallbladder damp-heat with an excess type condition. The prescription for the decoction is (5):

Gentiana

6 g

Scute

9 g

Gardenia

9 g

Alisma

12 g

Akebia

9 g

Plantago seed

9 g

Tang-kuei

3 g

Rehmannia, raw

9 g

Bupleurum

6 g

Licorice

6 g

This formula purges fire from both the liver and gallbladder and clears damp-heat accumulating in the lower warmer. It was first recorded in the Yifang Jijie (Analytic Collection of Medicinal Formulas; 1682) by Wang Ang, and, with its adoption as a standard reference formula during the 20th century, it displaced most other formulations from prior centuries that included gentiana. According to Qin Bowei, one of the leading physicians involved in the development of modern TCM: "In general, when there are symptoms of liver fire, Gentiana Combination with modifications can be relied upon (6)."

The only other formulas frequently referenced in modern Chinese literature with this herb are Danggui Longhui Wan (Tang-kuei, Gentiana, and Aloe Pill), a formula attributed to Zhu Danxi in the book Danxi Xinfa (ca. 1340), and Xieqing Wan (Drain the Green Pill, referring to clearing heat from the wood element), a pediatric formula by Qian Yi, the author of Rehmannia Six Formula (ca. 1100). Danxi's formula includes the strong laxatives aloe and rhubarb, and the rare musk gland, making it impractical for modern uses. It was prescribed for excessive fire of the liver and gallbladder leading to more severe symptoms than those for which Gentiana Combination might be given, and for cases accompanied by abdominal fullness, constipation, and scanty urine. It is possible that Longdan Xiegan Tang was designed as a replacement for this older formula, as they both contain gentiana, gardenia, scute, and tang-kuei. Yi's pediatric formula also included gentiana, gardenia, and tang-kuei. It was indicated for infantile convulsions, irritability, and insomnia accompanied by constipation (treated by rhubarb).

Chin-chiu is included in several traditional prescriptions for treating fever and inflammation in persons with deficiency syndrome. For this purpose, it is usually combined with ching-hao (qinghao; Artemisia annua) to help purge heat from the gallbladder. Ching-hao not only clears heat, it also has a fragrant quality associated with regulating the flow of qi in the liver and gallbladder. From the perspective of Chinese medical theory, the heat syndrome that is treated by these herbs is one in which deficiency comes first: this deficiency is understood to give rise to the fire (because the yin essence doesn't control it). From the Western viewpoint, the diseases being treated by these herbs can cause one to become quite weak.

A good example of the formulas with chin-chiu and ching-hao is, Qinggu San (qing = to cleanse; specifically, to cleanse heat; gu = bone; san = powder; hence, the powder to clear heat from the bone). The prescription is:

Stellaria

5 g

Picrorrhiza

3 g

Chin-chiu

3 g

Turtle shell

3 g

Lycium bark

3 g

Ching-hao

3 g

Anemarrhena

3 g

Licorice

2 g

The herbs stellaria, picrorrhiza, lycium bark, and anemarrhena are used in the treatment of deficiency heat syndromes. Turtle shell helps treat the deficiency by nourishing yin and blood; it also lowers fire and prevents bleeding due to heat agitating the blood. The most severe form of disorder treated by this formula is described as a "steaming sensation in the bone." The deficiency syndrome is marked by a thin pulse, and a dry reddish tongue, fatigue, and ease of sweating.

Other formulas that are of similar nature are Qinjiao Fulei Tang (Decoction with Chin-chiu to Support the Lungs), Qinjiao Biejia San (Powder of Chin-chiu and Turtle Shell), and Huangqi Beijie San (Powder of Astragalus and Turtle Shell). These formulas all include chin-chiu, lycium bark, and turtle shell to clear heat and alleviate the "bone-steaming fever." Qinjiao Biejia San also includes ching-hao. These formulas were originally designed to treat tuberculosis and similar disease patterns; they were adopted into Kampo (Japanese herbal medicine) and are still mentioned in modern Chinese herb texts (7, 8).

The best-known arthritis formula with chin-chiu is Duhuo Jisheng Tang (Tu-huo and Loranthus Combination); the herb is also a key ingredient in Da Qinjiao Tang (Major Chin-chiu Combination), used for apoplexy and paralysis. These two are similar formulations with a large number of ingredients, many of them tonics, in which chin-chiu plays a modest role: it is the ingredient in largest amount in Da Qinjiao Tang, making up 15% of the formula; it contributes to 7.5% of Duhuo Jisheng Tang. Although arthritis and apoplexy are very different disorders, in the Chinese medical view, both are engendered by wind that penetrates the vessels that are not full of qi and blood; these formulas are both indicated for patients who have a deficiency syndrome.

MODERN EVALUATIONS

The botanical origin of chin-chiu is mainly Gentiana macrophylla, but other sources include G. tibetica, G. straminea, G. crassicaulis, and G. dahurica. Gentiana (longdancao) is mainly derived from G. scabra, but is also obtained from G. triflora and G. regescens. The roots are the part used for both herb materials, and they are collected in the spring and fall seasons (9, 10).

The dominant active components in the Gentiana genus, including both chin-chiu and gentiana, are the secoiridoid glycosides, mainly gentiopicroside (see Figure 5), with lesser amounts of sweroside and swertiamarin (named for another genus of the Gentianacea, Swertia, where they were first found). The secoiridoids and iridoids of similar structure form the largest class of naturally-occurring monoterpenes. They are well represented not only in this genus, but throughout the Gentianaceae Family, and are responsible for their bitter taste (11). Formerly, it was reported that chin-chiu contained alkaloids, but it was later found that these compounds (e.g., gentianine) were artifacts generated during extraction and isolation of the compounds when ammonia was introduced and served as a nitrogen source (10). There are no significant amounts of alkaloids in the herbs.

Recent analysis (12) of an extract of the roots of Gentiana macrophylla revealed two novel and six known secoiridoids, along with kurarinone and kushenol (flavonoids also found in sophora root, kushen) and isovitexin (a flavonoid, named for its occurrence in vitex). Other components were the oily materials beta-sitosterol, stigmasterol, daucosterol, and beta-sitosterol-3-O-gentiobioside (these are all sterols, fatty components with anti-inflammatory activity found in numerous plants) and oleanolic acid (a basic triterpene).

Gentiana scabra, the main source of longdancao, has the highest gentopicroside concentration in the fall during the third year of growth, reaching 7.8% in the roots (only about 1% in the above-ground portions). Other species collected for this herb have lower amounts, ranging from 1.8% to 6.7%. Gentiana macrophylla and Gentiana dahurica, two major sources of chin-chiu, have only 0.2-1.4% gentopicroside (10). These differences in content explain why gentiana is considered a much stronger herb than chin-chiu and why Gentiana scabra is the desired source for gentiana.

The biological and pharmacological effects of the secoiridoids include stomachic, choleretic (promotes bile flow), and antihepatotoxic activities (11). These functions explain the traditional use of the herbs in treating hepatitis. Secoiridoids are found also in cornus (shanzhuyu), swertia (zhangyacai), patrinia (baijiangcao), and lonicera (jinyinhua), which are also included in treatments for hepatitis. In addition, these constituents have anti-inflammatory, antifungal, and antihistamine activities (9, 10, 12, 13).

Pharmacology studies of gentiopicroside include recent tests for therapeutic effects on two hepatic injury models, chemical and immunological (14). An increase in serum level of hepatic enzymes induced by oral treatment of carbon tetrachloride was suppressed by pretreatment with gentiopicroside at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an intravenous infusion of lipopolysaccharide (in mice primed with bacteria to yield an autoimmune hepatitis) was also inhibited by gentiopicroside pretreatment at the same dose. In the latter case, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum of control animals with a peak at 90-120 minutes following administration, then followed by an increase of the serum liver enzyme levels. Gentiopicroside significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting it protected against hepatitic inflammation by inhibiting the production of TNF. It is known that TNF-alpha-and possibly other related cytokines-are involved in the perpetuation of the inflammatory cascades in autoimmune diseases. Blockade of TNF-alpha leads to rapid improvement of rheumatoid arthritis disease activity and can prevent tissue destruction. TNF-alpha appears to also be involved in the inflammatory stage of lupus.

In the treatment of viral hepatitis (mainly hepatitis A and B), a formula known as Ku Jiao Tang (Sophora and Chin-chiu Decoction) was administered in 86 patients (15). The formula was comprised of chin-chiu, sophora, salvia, and serissa (liuyuexue). According to the clinical report, administration of the decoction twice per day normalized liver enzymes in 11-36 days of treatment.

In the treatment of systemic lupus erythematosus (SLE), 81 patients were treated with either Compound Qinjiao Tablet, prednisone, or the combination of the two (16). The tablet is comprised of chin-chiu, zaocys, astragalus, scrophularia, rehmannia, salvia, hoelen, alisma, and phellodendron. When given alone (54 patients), it was administered at 5 tablets, three times per day; in combined therapy (8 patients), it was administered at 10 tablets, twice per day with prednisone at 10-30 mg per day. As controls (19 patients), prednisone was given without the herbs. Treatment time averaged 9.3 months for the herb groups and 7.3 months for the control group. Among the 54 cases treated by herbs alone, it was reported that all but 12 cases improved and in the combined therapy group all cases improved; in the control group, all but one case had improved. However, in the herb groups, there were a higher proportion of cases going into complete remission. Further, the herb treatment was reported to be more effective for the improvement of nephropathy, arthralgia, and erythema, and for restoring normal erythrocyte sedimentation rate and complement (C3) levels than prednisone alone. No apparent side effects of the herb treatment were found in this observation.

In another trial for treatment of lupus (17), patients received combination treatment with prednisone and Lingdan Pian, which was composed of chin-chiu, ching-hao, moutan, turtle shell, buffalo horn, rehmannia, licorice, scrophularia, and other herbs. Each tablet contained 0.5 g crude herbs, given at 5 tablets a time, 3 times per day. As in the above trial, the use of the herb with prednisone was reported to produce better results, and fewer side effects, than prednisone alone. Rehmannia and scrophularia contain iridoid glycosides, which have similar pharmacological action as the secoiridoids. In a screening of 29 Chinese medicinal materials for immunomodulatory action, 14 showed significant effects, including chin-chiu, cornus, hoelen, and turtle shell (18), which may help explain the apparently favorable action of these formulas in treating lupus.

SUMMARY

Chin-chiu and gentiana are related herbs from the same genus (Gentiana) that have similar chemical constituents and overlapping actions and uses. Chin-chiu is traditionally administered for cases of yin deficiency heat and rheumatism, while gentiana is traditionally used for cases of liver fire and liver/gallbladder damp-heat. Gentiana Combination has become the standard formula referenced for liver fire syndromes of the excess type; there are a number of formulas with chin-chiu mentioned in the literature, but the ones with ching-hao and turtle shell are most often mentioned for treatment of deficiency heat syndromes.

One of the significant differences between these herbs, from the modern viewpoint, is the amount of the main bitter principals, the secoiridoids, which are far higher in gentiana than in chin-chiu. With the lower amount of secoiridoids in chin-chiu, the effects of other components, such as flavonoids, may be more notable. The active constituents, including iridoids, flavonoids, and oily compounds, have anti-inflammatory properties. Chin-chiu, in particular, has gained increasing use in treatment of autoimmune disorders: in addition to the long-standing tradition of treating rheumatoid arthritis, it is now often administered for lupus.